High-Throughput Sequencing Reveals the Incomplete, Short-Term Recovery of Infant Gut Microbiota following Parenteral Antibiotic Treatment with Ampicillin and Gentamicin

Abstract

ABSTRACTThe infant gut microbiota undergoes dramatic changes during the first 2 years of life. The acquisition and development of this population can be influenced by numerous factors, and antibiotic treatment has been suggested as one of the most significant. Despite this, however, there have been relatively few studies which have investigated the short-term recovery of the infant gut microbiota following antibiotic treatment. The aim of this study was to use high-throughput sequencing (employing both 16S rRNA andrpoB-specific primers) and quantitative PCR to compare the gut microbiota of nine infants who underwent parenteral antibiotic treatment with ampicillin and gentamicin (within 48 h of birth), 4 and 8 weeks after the conclusion of treatment, relative to that of nine matched healthy controls. The investigation revealed that the gut microbiota of the antibiotic-treated infants had significantly higher proportions ofProteobacteria(P= 0.0049) and significantly lower proportions ofActinobacteria(P= 0.00001) (and the associated genusBifidobacterium[P= 0.0132]) as well as the genusLactobacillus(P= 0.0182) than the untreated controls 4 weeks after the cessation of treatment. By week 8, theProteobacterialevels remained significantly higher in the treated infants (P= 0.0049), but theActinobacteria,Bifidobacterium, andLactobacilluslevels had recovered and were similar to those in the control samples. Despite this recovery of totalBifidobacteriumnumbers,rpoB-targeted pyrosequencing revealed that the number of differentBifidobacteriumspecies present in the antibiotic-treated infants was reduced. It is thus apparent that the combined use of ampicillin and gentamicin in early life can have significant effects on the evolution of the infant gut microbiota, the long-term health implications of which remain unknown.